The diagnosis, and thus therapy, of solid tumors of childhood is often difficult due to lack of distinguishing characteristics. This is especially true of Ewing's sarcoma, neuroblastoma, primitive soft tissue sarcomas, and (occasionally) lymphoma. We have evaluated the presence of a specific neuronal enzyme, neurone- specific enolase (NSE), in paraffin-embedded sections of a diverse group of solid childhood tumors, including previously unrecognized variants of neural tumors, employing immunocytochemistry with antisera to NSE. We find uniform reactivity of all neural tumors with this antibody. No cross- reactivity with non-neural tumors, save a rare example of differentiated rhabdomyosarcoma, was found. We conclude that NSE is a reliable, readily detected marker in even primitive childhood tumors of neural origin. Also, we have defined the neural histogenesis of a newly described, "round cell" tumor of chest wall resembling Ewing's sarcoma, the so-called Askin tumor, which in reality is a form of peripheral neuroepithelioma. Finally, we have recently confirmed the unique character of so- called peripheral neuroepithelioma, which is NSE-positive but which displays hybrid neural and Schwannian morphologic characteristics.